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Purpose: Small-cell esophageal carcinoma (SCEC) is a rare disease for which standard therapy has not yet been established. We report the results of three cases of limited-stage SCEC treated with combination therapy using carboplatin (CBDCA) and etoposide (VP-16) and radiotherapy.Materials and Methods: The clinical stage according to the Japanese Classification of Esophageal Cancer 7th ed. was stage III in 2 cases and stage IVa in 1. These patients with limited-stage SCEC were treated at our institution with four cycles of CBDCA and VP-16, either concurrent with radiotherapy for the second two cycles (n = 2) or followed by radiotherapy after the last cycle (n = 1).Results: A complete response (CR) was obtained for all three patients, resulting in a response rate of 100%. Two patients are alive at 16.4 and 22.5 months after initial treatment. One patient died with myeloid leukemia at 43.5 months after initial treatment. None of the patients had loco-regional recurrence. Brain metastasis was detected in one patient at 7 months after initial therapy and was treated with stereotactic radiotherapy combined with whole brain irradiation.Conclusion: CBDCA and VP-16 in combination with radiotherapy should be considered an important treatment option for SCEC. [ABSTRACT FROM AUTHOR]

Various animal and plant species exhibit allometric relationships among their respective traits, wherein one trait undergoes expansion as a power-law function of another due to constraints acting on growth processes. For instance, the acknowledged consensus posits that tree height scales with the two-thirds power of stem diameter. In the context of human development, it is posited that body weight scales with the second power of height. This prevalent allometric relationship derives its nomenclature from fitting two variables linearly within a logarithmic framework, thus giving rise to the term "power-law relationship." Here, we challenge the conventional assumption that a singular power-law equation adequately encapsulates the allometric relationship between any two traits. We strategically leverage quantile regression analysis to demonstrate that the scaling exponent characterizing this power-law relationship is contingent upon the centile within these traits' distributions. This observation fundamentally underscores the proposition that individuals occupying disparate segments of the distribution may employ distinct growth strategies, as indicated by distinct power-law exponents. We introduce the innovative concept of "multi-scale allometry" to encapsulate this newfound insight. Through a comprehensive reevaluation of (i) the height-weight relationship within a cohort comprising 7, 863, 520 Japanese children aged 5-17 years for which the age, sex, height, and weight were recorded as part of a national study, (ii) the stem-diameter-height and crown-radius-height relationships within an expansive sample of 498, 838 georeferenced and taxonomically standardized records of individual trees spanning diverse geographical locations, and (iii) the brain-size-body-size relationship within an extensive dataset encompassing 1, 552 mammalian species, we resolutely substantiate the viability of multi-scale allometric analysis. This empirical substantiation advocates a paradigm shift from uni-scaling to multi-scaling allometric modeling, thereby affording greater prominence to the inherent growth processes that underlie the morphological diversity evident throughout the living world., (© 2024. The Author(s).)

The body mass index (BMI), defined as weight in kilograms divided by height in meters squared, has been widely used to assess thinness and obesity in all age groups, including children and adolescents. However, the validity and utility of BMI as a reliable measure of nutritional health have been questioned. This study discusses the mathematical conditions that support the validity of BMI based on population statistics. Here, we propose a condition defined as allometric uni-scaling to ensure the validity of BMI as an objective height-adjusted measure. Any given centile curve, including the median curve, in a weight-for-height distribution should be approximated using power-law functions with the same scaling exponent. In contrast, when the scaling exponent varies depending on the position of the centile curve, it is called allometric multi-scaling. By introducing a method for testing these scaling properties using quantile regression, we analyzed a large-scale Japanese database that included 7,863,520 children aged 5-17 years. We demonstrated the remarkable multi-scaling properties at ages 5-13 years for males and 5-11 years for females, and the convergence to uni-scaling with a scaling exponent close to 2 as they approached 17 years of age for both sexes. We confirmed that conventional BMI is appropriate as an objective height-adjusted mass measure at least 17 years of age, close to adulthood, for both males and females. However, the validity of BMI could not be confirmed in younger age groups. Our findings indicate that the growth of children's weight-for-height relation is much more complex than previously assumed. Therefore, a single BMI-type formula cannot be used to assess thinness and obesity in children and adolescents., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Ogata et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background: Precision in evaluating underweight and overweight status among children and adolescents is paramount for averting health and developmental issues. Existing standards for these assessments have faced scrutiny regarding their validity. This study investigates the age and height dependencies within the international standards set by the International Obesity Task Force (IOTF), relying on body mass index (BMI), and contrasts them with Japanese standards utilizing the percentage of overweight (POW)., Method: We scrutinized a comprehensive database comprising 7,863,520 children aged 5-17 years, sourced from the School Health Statistics Research initiative conducted by Japan's Ministry of Education, Culture, Sports, Science, and Technology. Employing the quantile regression method, we dissected the structure of weight-for-height distributions across different ages and sexes, quantifying the potentially biased assessments of underweight and overweight status by conventional criteria., Results: Applying IOFT criteria for underweight assessment revealed pronounced height dependence in males aged 11-13 and females aged 10-11. Notably, a discernible bias emerged, wherein children in the lower 25th percentile were classified as underweight five times more frequently than those in the upper 25th percentile. Similarly, the overweight assessment displayed robust height dependence in males aged 8-11 and females aged 7-10, with children in the lower 25th percentile for height deemed obese four or five times more frequently than their counterparts in the upper 25th percentile. Furthermore, using the Japanese POW criteria for assessment revealed significant age dependence in addition to considerably underestimating the percentage of underweight and overweight cases under the age of seven. However, the height dependence for the POW criterion was smaller than the BMI criterion, and the difference between height classes was less than 3-fold., Conclusion: Our findings underscore the intricacies of age-dependent changes in body composition during the growth process in children, emphasizing the absence of gold standards for assessing underweight and overweight. Careful judgment is crucial in cases of short or tall stature at the same age, surpassing sole reliance on conventional criteria results., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Isoyama, Nose-Ogura, Ijitsu, Kruse, Nagai, Kayaba, Ogata, Mangalam and Kiyono.)

While the high year-round production of tomatoes has been facilitated by solar greenhouse cultivation, these yields readily fluctuate in response to changing environmental conditions. Mathematic modeling has been applied to forecast phenotypes of tomatoes using environmental measurements (e.g., temperature) as indirect parameters. In this study, metabolome data, as direct parameters reflecting plant internal status, were used to construct a predictive model of the anthesis rate of greenhouse tomatoes. Metabolome data were obtained from tomato leaves and used as variables for linear regression with the least absolute shrinkage and selection operator (LASSO) for prediction. The constructed model accurately predicted the anthesis rate, with an R 2 value of 0.85. Twenty-nine of the 161 metabolites were selected as candidate markers. The selected metabolites were further validated for their association with anthesis rates using the different metabolome datasets. To assess the importance of the selected metabolites in cultivation, the relationships between the metabolites and cultivation conditions were analyzed via correspondence analysis. Trigonelline, whose content did not exhibit a diurnal rhythm, displayed major contributions to the cultivation, and is thus a potential metabolic marker for predicting the anthesis rate. This study demonstrates that machine learning can be applied to metabolome data to identify metabolites indicative of agricultural traits., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Siriwach, Matsuzaki, Saito, Nishimura, Isozaki, Isoyama, Sato, Arita, Akaho, Higashide, Yano and Hirai.)

Rab guanosine triphosphatases in eukaryotic cells are key regulators of membrane-trafficking events, such as exocytosis and endocytosis. Rab7 regulates traffic from early to late endosomes and from late endosomes to vacuoles/lysosomes. The Rab7-interacting lysosomal protein (RILP) was extracted from the silkworm, Bombyx mori (B. mori), and expressed in Escherichia coli (E. coli), followed by its purification. The glutathione sulfotransferase pull-down assay revealed that Rab7 of B. mori interacted with RILP of B. mori. We then produced antibodies against RILP of B. mori in rabbits for their use in Western immunoblotting and immunohistochemistry. Western immunoblotting of brain tissue for RILP revealed a single band, at approximately 50 kD. RILP-like immunohistochemical reactivity (RILP-ir) was restricted to neurons of the pars intercerebralis and dorsolateral protocerebrum. Furthermore, RILP-ir was colocalized with the eclosion hormone-ir and bombyxin-ir. However, RILP-ir was not colocalized with prothoracicotropic hormone-ir. These results were similar to those of Rab7 from our previous study. These findings suggest that RILP and Rab7 are involved in the neurosecretion in a restricted subtype of neurons in B. mori. Thus, our study is the first to report of a possible relationship between an insect Rab effector and neurosecretion.

Recently, gene editing with transcription activator-like effector nucleases (TALENs) has been used in the life sciences. TALENs can be easily customized to recognize a specific DNA sequence and efficiently introduce double-strand breaks at the targeted genomic locus. Subsequent non-homologous end-joining repair leads to targeted gene disruption by base insertion, deletion, or both. Here, to readily evaluate the efficacy of TALENs in Xenopus laevis embryos, we performed the targeted gene disruption of tyrosinase (tyr) and pax6 genes that are involved in pigmentation and eye formation, respectively. We constructed TALENs targeting tyr and pax6 and injected their mRNAs into fertilized eggs at the one-cell stage. Expectedly, introduction of tyr TALEN mRNA resulted in drastic loss of pigmentation with high efficiency. Similarly, for pax6, TALENs led to deformed eyes in the injected embryos. We confirmed mutations of the target alleles by restriction enzyme digestion and sequence analyses of genomic PCR products. Surprisingly, not only biallelic but also paralogous, gene disruption was observed. Our results demonstrate that targeted gene disruption by TALENs provides a method comparable to antisense morpholinos in analyzing gene function in Xenopus F0 embryos, but also applies beyond embryogenesis to any life stage.

Rab proteins are small GTPases that play essential roles in vesicle transport. In this study, we examined the expression of Rab proteins and neuropeptide hormones in the brain of the silkworm, Bombyx mori. We produced antibodies against B. mori Rab1 and Rab14 in rabbits. Immunoblotting of samples of brain tissue from B. mori revealed a single band for each antibody. Rab1 and Rab14 immunohistochemical labeling in the brain of B. mori was restricted to neurons of the pars intercerebralis and dorsolateral protocerebrum. Rab1, Rab7 and Rab14 co-localized with bombyxin. Rab1 and Rab7 co-localized with eclosion hormone. Rab1 co-localized with prothoracicotropic hormone. These results suggest that Rab1, Rab7 and Rab14 may be involved in neuropeptide transport in the brain of B. mori. This is the first report on the specificity of Rab proteins for the secretion of different neuropeptides in insects.

Small GTPases of the Rab family are key regulators of membrane trafficking. We produced antibodies against the Rab7 protein of Bombyx mori (BRab7) in rabbits, and against the Rab11 protein of B. mori (BRab11) in mice. The antibodies recognized BRab7 and BRab11 proteins, but did not recognize other Rab proteins. Immunoblotting of samples from brain tissue of B. mori revealed a single band for each antibody. Rab11 was expressed in most tissues, whereas Rab7 was expressed in the brain, ovary, and testis. Immunohistochemical reactivity of Rab7 and Rab11 in the brain of B. mori was restricted to neurons of the pars intercerebralis and dorsolateral protocerebrum. Double-labeling experiments demonstrated that immunohistochemical reactivity of Rab7 co-localized with that of Rab11 and partially with that of Rab8. Immunohistochemical reactivity of Rab11 and Rab8 co-localized with that of PERIOD, one of the proteins associated with circadian rhythm. These findings suggest that Rab7, Rab8, and Rab11 are involved in protein transport in the neurons of the brain of B. mori and might play a role in the control of circadian rhythm.

Rab GTPases are essential for vesicular transport, whereas adenosine triphosphate (ATP) is the most important and versatile of the activated carriers in the cell. But there are little reports to clarify the connection between ATP and Rab GTPases. A cDNA clone (Rab14) from Bombyx mori was expressed in Escherichia coli as a glutathione S-transferase fusion protein and purified. The protein bound to [(3)H]-GDP and [(35)S]-GTPgammaS. Binding of [(35)S]-GTPgammaS was inhibited by guanosine diphosphate (GDP), guanosine triphosphate (GTP) and ATP. Rab14 showed GTP- and ATP-hydrolysis activity. The Km value of Rab14 for ATP was lower than that for GTP. Human Rab14 also showed an ATPase activity. Furthermore, bound [(3)H]-GDP was exchanged efficiently with GTP and ATP. These results suggest that Rab14 is an ATPase as well as GTPase and gives Rab14 an exciting integrative function between cell metabolic status and membrane trafficking.

Lateral crossbite on mixed dentition does not always cause facial asymmetry or functionally abnormal movement of the mandible in children. However, it is often observed that facial asymmetry will worsen during growth in the absence of orthodontic treatment. In adult cases, lateral crossbite is one of the etiological factors of temporomandibular joint disorder. This case report presents two cases of lateral crossbite of mixed dentition. The terms of treatment were shorter than those in cases with permanent dentition. Also, methods of treatment were simpler, and the patients developed favorably. The opposite results were obtained in cases of permanent dentition.

The purpose of this survey was to investigate the symptoms of temporomandibular joint disorders (TMD) in orthodontic patients and to define the relationships between symptoms and malocclusion and/or orthodontic treatment. The subjects were 532 patients, 6 to 38 year old Japanese, in the orthodontic department of Tokyo Dental College Hospital. They were examined for past or recent TMJ sounds, pain in the TMJ area, and abnormal jaw movements. The prevalence of TMJ symptoms was 33.8%. Sex differences were not statistically significant. The prevalence of TMD symptoms increased with age. TMD symptoms in young orthodontic patients (6-18 years old) were more common than in untreated subjects. Posterior crossbite and open bite patients had a high prevalence of symptoms.